Abstract

PURPOSE OF REVIEW: Several large studies have shown increased mortality due to all-causes and to atherosclerotic cardiovascular disease. In most clinical settings, plasma HDL-cholesterol is determined as a sum of free cholesterol and cholesteryl ester, two molecules with vastly different metabolic itineraries. We examine the evidence supporting the concept that the pathological effects of elevations of plasma HDL-cholesterol are due to high levels of the free cholesterol component of HDL-C. RECENT FINDINGS: In a small population of humans, a high plasma HDL-cholesterol is associated with increased mortality. Similar observations in the HDL-receptor deficient mouse (Scarb1 -/- ), a preclinical model of elevated HDL-C, suggests that the pathological component of HDL in these patients is an elevated plasma HDL-FC. SUMMARY: Collective consideration of the human and mouse data suggests that clinical trials, especially in the setting of high plasma HDL, should measure free cholesterol and cholesteryl esters and not just total cholesterol.

Original languageEnglish (US)
Article numberPMID: 37732779
Pages (from-to)278-286
Number of pages9
JournalCurrent opinion in lipidology
Volume34
Issue number6
DOIs
StatePublished - Dec 1 2023

Keywords

  • Humans
  • Animals
  • Mice
  • Cholesterol, HDL
  • Cholesterol Esters/metabolism
  • Cholesterol
  • Hypercholesterolemia
  • Atherosclerosis/genetics
  • Cholesterol Ester Transfer Proteins
  • atherosclerosis
  • free cholesterol
  • high-density lipoproteins
  • probucol
  • serum opacity factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics
  • Molecular Biology
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism
  • Cell Biology

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